A phase II trial of lenvatinib in patients with metastatic colorectal cancer after standard chemotherapy - A phase II trial of lenvatinib in patients with metastatic colorectal cancer after standard chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
研究概览
简要总结
Two recent international phase 3 studies reported that regorafenib or trifluridine/tipiracil provided significant improvements in DCR, PFS and OS, compared with placebo, in patients with metastatic colorectal cancer after failure of standard chemotherapies (DCR; 41%, median PFS; 1.9 months, median OS; 6.4 months in the CORRECT study, and DCR; 44%, median PFS; 2.0 months, median OS; 7.1 months in the RECOURSE study). Interestingly, the present single-arm phase 2 study of lenvatinib revealed favorable DCR and median PFS values in patients with metastatic colorectal cancer, compared with those in the regorafenib or trifluridine/tipiracil study. The most common adverse events were hypertension, proteinuria, thrombocytopenia, and fatigue, while the most case of grade 2 or 3 hypertension and proteinuria required treatment interruption and dose reduction. Most patients with metastatic colorectal cancer in the salvage-line setting had grade 1 or 2 proteinuria and hypertension at baseline because of the long-term prior treatment with anti-VEGF/VEGFR treatment. Therefore, it was suggested that those adverse events and dose reductions were higher than those of trials for the other cancer. Although palmar-plantar erythrodysesthesia is a not life-threatening toxicity, these adverse events have a significant impact on treatment schedules and quality of life in treated patients. More than Grade 3 palmar-plantar erythrodysesthesia has been observed in 0% of patients treated with lenvatinib in this study, while 28% in patients treated with regorafenib in the CORRECT Japanese population. To date, the clear mechanism of palmar-plantar erythrodysesthesia by VEGF receptor tyrosine kinase inhibitors is not known, but it has been reproduced that palmar-plantar erythrodysesthesia by lenvatinib is well tolerated. Overall, it is suggested that lenvatinib might be a favorable treatment option in terms of toxicities.
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- >= 20age old 至 <= 79age old（—）
- 性别
- All
入选标准
- •1)Pathologically proven colorectal adenocarcinoma
- •2)Unresectable metastatic colorectal cancer (except for appendiceal and anal canal cancer)
- •3)Refractory or intolerable to all of the following standard chemotherapy
- •a.Fluoropyrimidines,oxaliplatin,irinotecan and bevacizumab
- •b.Cetuximab or panitumumab in patients with RAS wild-type
- •4)No symptomatic brain metastasis and carcinomatous meningitis
- •5)Oral intake
- •6)Aged 20 to 79 years
- •7)Performance Status 0 or 1
- •8)One or more measurable lesions confirmed by contrast enhanced CT
- •9)No prior treatment of lenvatinib and regorafenib
- •10)Not received anti-cancer therapy within 14days before registration
- •11)Adequately controlled blood pressure
- •12)Not having any of the following histories/complications
- •a.History of hypertensive crisis or hypertensive encephalopathy
- •b.History of total gastrectomy
- •c.History of surgery under general anesthesia or laparotomy biopsy within 28days before registration
- •d.Unrecovered wound,active gastrointestinal ulcer or bleeding from the primary lesion
- •e.History of congenital hemorrhagic diathesis or coagulation disorder
- •f.Cardiovascular diseases requiring more than 325mg of aspirin daily
- •13)Adequate organ functions defined as below within 14days before registration
- •a.Neutrophil count >=1500/mm3
- •b.Platelet count >=100000/mm3
- •c.Hemoglobin >=8.5g/dL
- •d.Total bilirubin <=1.8mg/dL
- •e.AST(GOT)<=100U/L (<=150U/L with liver metastases)
- •f.ALT(GPT)<=100U/L (<=150U/L with liver metastases)
- •g.Creatinine <=1.5mg/dL
- •h.PT-INR <=1.5(<=3.0 in patients receiving any prophylactic anticoagulant agents)
- •i.Adequate proteinuria value defined
- •i)Negative or 1+ on urine dipstick testing
- •ii)When >2+ on urine dipstick testing, <=1g/24hr by 24hr urine collection
- •14)Given consent to contraception
- •15)Written informed consent
排除标准
- •1)Active double cancer; synchronous or metachronous within 5years. Patients with carcinoma in situ are eligible
- •2)Infections requiring systemic therapy
- •3)Fever of >=38 degrees Celsius at the time of registration
- •4)Grade >=2 adverse reactions caused by prior therapy except any grade of alopecia and grade 2 peripheral neurotoxicity
- •5)Pregnant or breast-feeding women,or women suspected of being pregnant
- •6)Mental disease interfering taking part in the trial
- •7)Taking continuous systemic steroids and/or other immunosuppressive drugs(orally or intravenously)
- •8)HIV antibody positive
- •9)Interstitial pneumonia and/or pulmonary fibrosis and/or severe pulmonary emphysema diagnosed by chest CT imaging
- •10)History of any of the followings; unstable angina within 6 months before registration,heart attack,pulmonary embolism,deep vein thrombosis,brain bleeding,cerebral infarction,transient ischemic attacks within 6 months before registration and arterial thromboembolism